# US 2018/0021376 A1 · Naming of KH1 through KH55 good healthy cells synthesizes the KH1 through KH55 proteins

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- Number: US 2018/0021376 A1
- Document ID: US20180021376A1
- Status: Published application
- Kind: A1
- Application number: 15/355,304
- Filed: 2015-05-28
- Published: 2018-01-25
- Earliest claimed: 2011-03-04
- Assignees: Rare Antibody Antigen Supply, Inc.
- Applicants: Rare Antibody Antigen Supply, Inc.
- Inventors: Kieu Hoang
- Web page: https://patentgrep.com/patent/US20180021376A1

## CPC

- A61K 35/16: Blood plasma; Blood serum (umbilical cord blood A61K35/51)
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 38/16: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)}
- A61K 38/36: Blood coagulation or fibrinolysis factors
- A61K 38/363: {Fibrinogen}
- A61K 38/4833: {Thrombin (3.4.21.5)}
- A61L 24/106: {Fibrin; Fibrinogen}
- A61P 31/20: for DNA viruses
- C07K 14/75: Fibrinogen
- C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C07K 16/06: from serum
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 2039/505: {comprising antibodies}
- C07K 2317/70: characterized by effect upon binding to a cell or to an antigen
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present invention provides purified blood plasma products from fraction II+III containing proteins at concentrations useful for the treatment of various diseases and infections including hepatitis B virus. Methods of manufacture and treatment are also provided. The purified blood plasma products regulate levels of immune cells and their proteins in the organs and peripheral blood of treated subjects. Examples of immune cells and associated proteins regulated by the purified blood plasma products include CD62L levels on T cells, CD4+, CD8+, CD28+, and Foxp3+ T cells, B cells, as well as granulocytes and macrophages.

## Claims

### Claim 1

An isolated purified IVIG plasma product comprising an isolated purified protein complex containing proteins defined by amino acid sequences SEQ ID NOs 33-37.

### Claim 2 (depends on 1)

The isolated purified protein complex of claim 1 further comprising proteins defined by amino acid sequences SEQ ID NOs 22-31.

### Claim 3 (depends on 1)

The isolated purified protein complex of claim 1 further comprising a protein defined by amino acid sequence SEQ ID NO: 51.

### Claim 4

An isolated purified IVIG plasma product comprising an isolated purified protein complex containing:
a first substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 22;
a second substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 23;
a third substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 24;
a fourth substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 25;
a fifth substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 26;
a sixth substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 27;
a seventh substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 28;
an eighth substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 29;
a ninth substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 30;
a tenth substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 31;
an eleventh substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 32;
a twelfth substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 33;
a thirteenth substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 34;
a fourteenth substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 35;
a fifteenth substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 36; and
a sixteenth substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 37.

### Claim 5

An isolated purified IVIG plasma product comprising an isolated purified protein complex containing:
a first substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 33;
a second substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 34;
a third substantially pure protein having at least 90% homology to amino acid SEQ ID NO: 35;
a fourth substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 36; and
a fifth substantially pure protein having at least 90% homology to amino acid sequence SEQ ID NO: 37.

### Claim 6

An isolated purified IVIG plasma product comprising an isolated purified protein complex containing:
a first substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 22, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 22;
a second substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 23, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 23;
a third substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 24, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 24;
a fourth substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 25, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 25;
a fifth substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 26, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 26;
a sixth substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 27, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 27;
a seventh substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 28, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 28;
an eighth substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 29, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 29;
a ninth substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 30, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 30;
a tenth substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 31, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 31;
an eleventh substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 32, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 32;
a twelfth substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 33, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 33;
a thirteenth substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 34, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 34;
a fourteenth substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 35, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 35;
a fifteenth substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 36, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 36; and
a sixteenth substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 37, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 37.

### Claim 7

An isolated purified IVIG plasma product comprising an isolated purified protein complex containing:
a first substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 33, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 33;
a second substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 34, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 34;
a third substantially pure protein having at least 80% homology to amino acid SEQ ID NO: 35, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 35;
a fourth substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 36, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 36; and
a fifth substantially pure protein having at least 80% homology to amino acid sequence SEQ ID NO: 37, wherein said substantially pure protein has the same activity as the protein defined by amino acid sequence SEQ ID NO: 37.

### Claim 8 (depends on 1)

The isolated purified IVIG plasma product of claim 1 wherein the proteins defined by amino acid sequences SEQ ID NOs 33-37 have a concentration of at least 30%.

### Claim 9 (depends on 2)

The isolated purified IVIG plasma product of claim 2 wherein the proteins defined by amino acid sequences SEQ ID NOs 22-37 have a concentration of at least 30%.

### Claim 10 (depends on 3)

The isolated purified IVIG plasma product of claim 3 wherein the proteins defined by amino acid sequences SEQ ID NOs 22-37, and 51 have a concentration of at least 30%.

### Claim 11

A method of treating hepatitis B in a patient comprising:
administering to said patient an effective dose of an isolated purified IVIG plasma product, wherein the isolated purified IVIG plasma product comprises:
a first protein defined by amino acid sequence SEQ ID NO: 33;
a second protein defined by amino acid sequence SEQ ID NO: 34;
a third protein defined by amino acid sequence SEQ ID NO 35;
a fourth protein defined by amino acid sequence SEQ ID NO 36; and
a fifth protein defined by amino acid sequence SEQ ID NO 37.

### Claim 12 (depends on 11)

The method according to claim 11 wherein the isolated purified IVIG plasma product further comprises:
a sixth protein defined by amino acid sequence SEQ ID NO: 22;
a seventh protein defined by amino acid sequence SEQ ID NO: 23;
an eighth protein defined by amino acid sequence SEQ ID NO: 24;
a ninth protein defined by amino acid sequence SEQ ID NO: 25;
a tenth protein defined by amino acid sequence SEQ ID NO: 26;
an eleventh protein defined by amino acid sequence SEQ ID NO: 27;
a twelfth protein defined by amino acid sequence SEQ ID NO: 28;
a thirteenth protein defined by amino acid sequence SEQ ID NO: 29;
a fourteenth protein defined by amino acid sequence SEQ ID NO: 30;
a fifteenth protein defined by amino acid sequence SEQ ID NO: 31; and
a sixteenth protein defined by amino acid sequence SEQ ID NO: 32.

### Claim 13 (depends on 12)

The method according to claim 12 wherein the isolated IVIG plasma product further comprises a sixteenth protein defined by amino acid sequence SEQ ID NO: 51.

### Claim 14 (depends on 13)

The method according to claim 13 wherein CD62L is regulated to an effective range on CD4+ T cells in peripheral blood of a hepatitis B patient for treating HBV.

### Claim 15 (depends on 13)

The method according to claim 13 wherein CD62L is regulated to an effective range on CD4+ T cells in the spleen of a hepatitis B patient for treating HBV.

### Claim 16 (depends on 13)

The method according to claim 13 wherein CD62L is regulated to an effective range on CD8+ T cells in peripheral blood of a hepatitis B patient for treating HBV.

### Claim 17 (depends on 13)

The method according to claim 13 wherein CD62L is regulated to an effective range on CD8+ T cells in the spleen of a hepatitis B patient for treating HBV.

### Claim 18 (depends on 13)

The method according to claim 13 wherein levels of CD4+ T cells are regulated to an effective range in peripheral blood of a hepatitis B patient for treating HBV.

### Claim 19 (depends on 13)

The method according to claim 13 wherein levels of CD4+ T cells are regulated to an effective range in the spleen of a hepatitis B patient for treating HBV.

### Claim 20 (depends on 13)

The method according to claim 13 wherein levels of CD28+ T cells are regulated to an effective range in peripheral blood of a hepatitis B patient for treating HBV.

### Claim 21 (depends on 13)

The method according to claim 13 wherein levels of CD28+ T cells are regulated to an effective range in the spleen of a hepatitis B patient for treating HBV.

### Claim 22 (depends on 13)

The method according to claim 13 wherein levels of Foxp3+ T cells are regulated to an effective range in the spleen of a hepatitis B patient for treating HBV.

### Claim 23 (depends on 13)

The method according to claim 13 wherein levels of Foxp3+ T cells are regulated to an effective range on T cells in peripheral blood of a hepatitis B patient for treating HBV.

### Claim 24 (depends on 13)

The method according to claim 13 wherein levels of CD28+ T cells are regulated to an effective range in the spleen of a hepatitis B patient for treating HBV.

### Claim 25 (depends on 13)

The method according to claim 13 wherein B cell levels are regulated to an effective range in the peripheral blood of a hepatitis B patient for treating HBV.

### Claim 26 (depends on 13)

The method according to claim 13 wherein B cell levels are regulated to an effective range in the spleen of a hepatitis B patient for treating HBV.

### Claim 27 (depends on 13)

The method according to claim 13 wherein granulocyte levels are regulated to an effective range in the peripheral blood of a hepatitis B patient for treating HBV.

### Claim 28 (depends on 13)

The method according to claim 13 wherein granulocyte levels are regulated to an effective range in the spleen of a hepatitis B patient for treating HBV.

### Claim 29 (depends on 13)

The method according to claim 13 wherein macrophage levels are regulated to an effective range in the peripheral blood of a hepatitis B patient for treating HBV.

### Claim 30 (depends on 13)

The method according to claim 13 wherein macrophage levels are regulated to an effective range in the spleen of a hepatitis B patient for treating HBV.

### Claim 31

A method of manufacturing an isolated purified IVIG plasma product containing proteins defined by amino acid sequences SEQ ID NOs 33-37 comprising:
a) obtaining a fraction II+III paste from human blood plasma;
b) suspending and diluting the fraction II+III paste at a ratio of 1:17;
c) adjusting the pH of the diluted fraction II+III paste to a pH of 5.2 to produce an adjusted fraction II+III paste;
d) adding ethanol to the adjusted fraction II+III paste to produce a 17% ethanol fraction II+III product;
e) press filtering the 17% ethanol fraction II+III product and collecting a filtrate comprising fraction III;
f) concentrating the filtrate by ultrafiltration to form a 100 k ultrafiltrate;
g) adjusting the pH of the 100 k ultrafiltrate to a pH of 4.0;
h) filtering the pH adjusted ultrafiltrate using a 0.45 um filter and collecting a filtered product; and
i) nanofiltrating the filtered product with a 50 nm filter to obtain a final product.

### Claim 32

A method of manufacturing an isolated purified IVIG plasma product containing proteins defined by amino acid sequences SEQ ID NOs 22-37 comprising:
a) obtaining a fraction II+III paste from human hepatitis B immune globulin having high levels of hepatitis B surface antigen;
b) suspending and diluting the fraction II+III paste at a ratio of 1:17;
c) adjusting the pH of the diluted fraction II+III paste to a pH of 5.2 to produce an adjusted fraction II+III paste;
d) adding ethanol to the adjusted fraction II+III paste to produce a 17% ethanol fraction II+III product;
e) press filtering the 17% ethanol fraction II+III product and collecting a filtrate comprising fraction III;
f) concentrating the filtrate by ultrafiltration to form a 100 k ultrafiltrate;
g) adjusting the pH of the 100 k ultrafiltrate to a pH of 4.0;
h) filtering the pH adjusted ultrafiltrate using a 0.45 um filter and collecting a filtered product; and
i) nanofiltrating the filtered product with a 50 nm filter to obtain a final product.

### Claim 33

A method of producing an isolated purified IVIG plasma product containing proteins defined by amino acid sequences SEQ ID NOs 22-37, and 51 comprising:
a) manufacturing a non-sterile final bulk of normal immunoglobulin;
b) manufacturing a non-sterile final bulk of hepatitis B immune globulin;
c) creating a immunoglobulin mixture comprising 80% of the non-sterile final bulk of normal immunoglobulin and 20% of the non-sterile final bulk of hepatitis B immune globulin;
d) performing sterile filtration on the immunoglobulin mixture and collecting a final product.